It can be desirable in the medical and veterinary arts to reduce fat accumulation in fat-storing cells (“adipocytes”). In obese human and non-human animals in particular, adipocytes that accumulate excess lipids can become insulin-resistant, a characteristic that has many adverse effects including the development of diabetes. Adipocytes cannot directly take up and accumulate triglycerides from the blood. Instead, an cell-associated extracellular lipoprotein lipase (LPL) enzyme breaks down blood-borne triglyceride molecules into a glycerol molecule and three fatty acids molecules. The adipocytes can take up and convert the fatty acids into triacylglycerides for accumulation and storage.
Likewise, adipocytes cannot directly secrete fatty acids. Instead, a intracellular hormone-sensitive lipase breaks down cellular triacylglycerides into free fatty acid and glycerol metabolites that can be released from the cells. Hormone-sensitive lipase activity increases and decreases in response to its phosphorylation by a cyclic AMP-dependent protein kinase. The extent of phosphorylation, in turn, is determined by cyclic AMP levels. Norepinephrine and glucagon stimulate cyclic AMP production while insulin decreases cyclic AMP levels.
Conjugated linoleic acid (CLA), a series of positional and geometric isomers having eighteen carbons and a pair of conjugated double bonds, has many biological activities including those related to the metabolism of body fat and arachidonic acid. CLA inhibits LPL activity and prevents fat accumulation in human and non-human animals. Other compounds and methods for controlling body fat by reducing accumulation of fat in fat cells are desired.
CLA also inhibits platelet aggregation, in that it inhibits cyclooxygenase (COX)-directed conversion of arachidonic acid to prostaglandins and thromboxanes. Thromboxane A2 is a potent inducer of platelet aggregation. Inhibition of platelet aggregation advantageously reduces the risk of arteriosclerosis, inflammation, and risk of stroke. Millions of Americans are prescribed aspirin to reduce the risk of these diseases. Other compounds and methods for inhibiting platelet aggregation are also desired.